Triethylamine → (R)-tert-butyl 1-(5-bromo-3-(2-cyanoacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 408374노트

반응식

HRID 408374 반응식
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.C(N(CC)CC)C.[NH2:29][C:30]1[C:38]2[C:33](=[N:34][CH:35]=[C:36]([Br:53])[C:37]=2[N:39]2[CH2:44][CH2:43][CH2:42][C@@H:41]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:40]2)[NH:32][CH:31]=1>CC#N.O.O.CN1C(=O)CCC1>[Br:53][C:36]1[C:37]([N:39]2[CH2:44][CH2:43][CH2:42][C@@H:41]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:50])([CH3:49])[CH3:51])[CH2:40]2)=[C:38]2[C:30]([NH:29][C:4](=[O:6])[CH2:3][C:1]#[N:2])=[CH:31][NH:32][C:33]2=[N:34][CH:35]=1

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 9740Cyanoacetic acidHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 67045407(R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

생성물 1

HCID 67045531(R)-tert-butyl 1-(5-bromo-3-(2-cyanoacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate수율 26%

시약·촉매·용매 3

HCID 962Water용매HCID 13387N-methyl-2-pyrrolidone용매HCID 18373917Acetonitrile--water (1/1)용매

실험 절차

2-Cyanoacetic acid (0.332 g, 3.90 mmol), BOP-Cl (0.993 g, 3.90 mmol), and triethylamine (1.02 mL, 7.31 mmol) were added to an NMP solution (2 mL) of (R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.200 g, 0.487 mmol; Example 98, Step A). The reaction was then stirred for 18 hours, then poured into water, and extracted with DCM. The combined organic fractions were dried (MgSO4), filtered, and concentrated to give the crude product, which was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 5-95% CH3CN/water) to give (R)-tert-butyl 1-(5-bromo-3-(2-cyanoacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.06 g, 26% yield).

후처리

  1. extractionextracted with DCM
  2. dry with materialThe combined organic fractions were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give the crude product, which
  6. customwas purified by reverse phase chromatography (Biotage SP4

출처 및 근거

ORD 기록
ord-66e79942bcc14dd0af9bfc5174f22d58
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08758830B2

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